Parenteral L-Arginine Improves Mitochondrial Function in Children with Sickle Cell Disease Admitted for Vaso-Occlusive Pain Episodes

Conclusion: These data demonstrate for the first time that Arg supplementation increases mitochondrial activity and decreases oxidative stress in children with SCD and VOE. Our prior study showed that complex V inhibition leads to increased mitochondrial oxidant production in platelets from SCD patients. The improvement in complex V function & decreased oxidative markers observed with Arg treatment are consistent with Arg-induced decrease in mitochondrial oxidant generation. However, Arg treatment potentially regulates other oxidant sources and could decrease overall oxidative stress in SCD patients. Arg therapy has been reported to improve symptoms associated with MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) suggesting an impact of arginine on mitochondrial activity that may be beneficial for patients with SCD. With the recent FDA approval of L-glutamine, which is an Arg prodrug, this is also a potential consequence of glutamine that warrants further study. This increase in mitochondrial function may mechanistically contribute to decreased pain and ultimately less opioid requirement after IV Arg treatment in SCD, as well as have further implications for improved metabolism and oxidative signaling in these patients.DisclosuresDampier: Pfizer: Research Funding. Morris: Pfizer: Consultancy; MAST Therapeutics: Research Funding; UCSF-Benioff Children's Hospital Oakland: Patents & Royalties: For nutritional supplement licensed ...

Source: Blood - November 21, 2018 Category: Hematology Authors: Shiva, S., Brown, L. A., Wang, Y., Dampier, C., Watt, A., Tripathi, V., Bhutta, A., Kumari, P., Figueroa, J., Zmitrovich, A., Morris, C. R. Tags: 114. Hemoglobinopathies, Excluding Thalassemia Clinical: Novel or Improved Approaches To Treating Sickle Cell Disease Source Type: research